Catheters, particularly intravenous (IV) catheters, are used for infusing fluid (such as saline solution, various medicaments and parenteral nutrition) into a patient, withdrawing blood from a patient and monitoring various parameters of the patient's vascular system. Generally, catheters include a lumen or reservoir which contains fluid or medication to be injected or dispensed into a patient's body and an injection port or device for access with a needle.
Complications associated with catheters include those related to their insertion, such as pneumo/hemothorax, arterial puncture, and nerve injury, and secondary problems occurring as a consequence of their use, such as thrombosis and infection. If a catheter becomes infected the patient will require additional treatment and perhaps removal of the catheter. In the case of transcutaneous catheters, skin penetration is a common route of infection. Catheter sepsis remains one of the major causes of morbidity and mortality in a patient receiving home parenteral nutrition. Implanted catheters can often become plugged or fouled over time. This is a problem with intravascular catheters, where clotting and thrombus formation within the catheter lumen can be problematic.
The majority of serious catheter-related infections are associated with central venous catheters (CVCs), especially those that are placed in patients in intensive care units (ICUs). In the ICU setting, the incidence of infection is often higher than in the less acute in-patient or ambulatory setting. Certain catheters (e.g., pulmonary artery catheters and peripheral arterial catheters) may be accessed multiple times per day for hemodynamic measurements or to obtain samples for laboratory analysis, augmenting the potential for contamination and subsequent clinical infection. A total of 250,000 cases of CVC-associated bloodstream infections (BSIs) have been estimated to occur annually, and the cost of CVC-associated BSI is substantial in terms of morbidity and in terms of financial resources expended.
To reduce problems associated with clotting and thrombus formation, it is now common to “lock” intravascular access catheters between successive uses. Locking typically involves first flushing the catheter with saline to remove blood and other substances from the catheter lumen. After the catheter has been flushed, an anti-coagulant solution, typically heparin, is then injected to displace the saline and fill the lumen. The heparin-locking solution prevents blood from entering the lumen and actively inhibits clotting and thrombus formation within the lumen. While some thrombus may still form at the distal tip of the catheter, the formation is usually minimal and presents few problems. It has further been proposed to combine various antimicrobial substances with the locking solution in order to inhibit infection at the same time that thrombus formation is being inhibited.
While generally effective, the use of heparin for catheter locking solutions suffers from a number of disadvantages. The need to prepare a heparin solution at the end of every catheter treatment session is time-consuming and presents an opportunity for caregiver error. Hemodialysis and hemofiltration patients may undergo such heparin locks at least several times a week, while patients on IV may have to undergo such heparin locks several times a day. The inconvenience and expense of performing heparin locks can be burdensome over time. Moreover, the need to combine a separate anti-microbial agent in the heparin lock solution further complicates the procedure and adds expense, and the addition of an anti-microbial agent to the heparin lock will generally be effective only within the lumen and at the openings from the lumen. There will be little reduction in the risk of infection in the regions surrounding the implanted catheter, including at the point of penetration through the skin where the risk of infection is the greatest. Some locking solutions have been designed to overcome this problem and to penetrate the material of the catheter to provide antimicrobial action in tissues surrounding the catheter.
U.S. Pat. No. 6,592,564 describes the use of lower alcohols for disinfecting implanted catheters. The alcohol diffuses through the porous material of the catheter or other implanted device, thereby providing antimicrobial activity to the surrounding tissue in addition to the interior of the device.
Alcohols are well-known for their disinfection properties. Rubbing alcohol containing 70% ethyl alcohol and 30% water, and isopropyl rubbing alcohol containing 70% isopropyl alcohol and 30% water are listed in the United States Pharmacopia (USP) official monograph XXIV, pages 60 and 927, respectively, as disinfectants. Recently published studies indicate that alcohol is a potent antimicrobial agent, and if used with surgical scrub, will cause significant mean log reduction of bacterial counts.
U.S. Pat. No. 6,350,251 discloses internal prosthetic devices such as catheters or ports including a biocidal lock comprising an anticoagulant and a non-antibiotic biocide.
In prior art compositions which are alcohol based, the alcohol evaporates very quickly or becomes diluted, and does not provide long-lasting antimicrobial activity. This results in the need for repeated flushing of the catheter and renewal of the antimicrobial composition when the time between uses of the catheter is long. There remains a need for an antimicrobial locking solution which can provide long-lasting action, without the need for additional applications in between uses of the catheter.